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Using Genetic Tools to Dissect Neural Circuits for Social Communication

使用遗传工具剖析社交沟通的神经回路

基本信息

批准号：
10405059
负责人：
Richard D Mooney
金额：
$ 51.77万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-07-11 至 2024-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10405059
关键词：
Acoustics Adult Affect Brain Calcium Chemicals Communication Data Disease Electrophysiology (science)Female Foundations Future Genetic Human Image Impairment Individual Influentials Link Mammals Maps Measures Medial Mediating Mental disorders Methods Midbrain structure Monitor Mus Neurodevelopmental Disorder Neurons Pattern Perception Play Prefrontal Cortex Production Research Role Schizophrenia Signal Transduction Social Environment Social Functioning Social Interaction Social Work Testing Ultrasonics autism spectrum disorder behavior measurement cortex mapping genetic approach imaging modality in vivo calcium imaging in vivo imaging innovation insight male midbrain central gray substance mind control mouse model neural circuit neuropsychiatric disorder novel optogenetics relating to nervous system response skills social social attachment social communication social deficits sound stem tool virus genetics vocalization

项目摘要

Project Summary An inability to form and maintain social bonds typifies a wide range of neuropsychiatric and neurodevelopmental disorders. These social deficits stem in large part from impaired expressive and receptive vocal communication skills. Surprisingly, exactly how vocal communication promotes social affiliation is not well understood, in part because the underlying neural circuits remain poorly described. Here we propose the use of a novel genetic approach to selectively tag neurons that are active during social encounters that elicit vocalizations. We will combine this innovative method with in vivo imaging, electrophysiology, chemical and optogenetic perturbations of neural activity, and behavioral measurements to identify neural circuits that facilitate expressive and receptive aspects of vocal communication in the service of social affiliation. In Aim 1, we will test the idea that a specific subpopulation of neurons in the midbrain periaqueductal gray (PAG) is required for male and female mice to produce vocalizations used during their social interactions. In Aim 2, we will manipulate the activity of these PAG neurons to suppress or augment vocalization, allowing us to test the idea that these vocalizations promote social affiliation. In Aim 3, we will test the idea that prefrontal cortical (PFC) neurons that provide input to PAG vocalization neurons are important in regulating vocalization as a function of social context. In Aim 4, we will either reversibly silence or image PFC neurons that provide input to the PAG to test the idea that they play a role in generating affiliative social responses in males and females listening to a vocalizing individual. These studies will identify the neurons and circuits that gate vocalization during social encounters and promote social affiliation in response to these acoustic signals. This research will also build the foundation for future studies that explore how these circuits are affected in mouse models of neuropsychiatric disorders characterized by social communication and affiliation deficits, such as autism spectrum disorder and schizophrenia.

项目总结